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Cardiac adaptation to high altitude in the plateau pika (Ochotona curzoniae).

ABSTRACT: The aim of this study was to assess maximal heart rate (HR) and heart morphological changes in high altitude living "plateau pikas" and rats bred at 2260 m. Rats and pikas were catheterized to measure HR (2260 m). After baseline measurements, 1 mg/kg of atropine (AT) and increasing doses of isoproterenol (IsoP) (0.1, 1, 10, and 100 ?g kg) were injected into animals. Right (RV) and left ventricles (LV) were removed to calculate Fulton's ratio (LV + septum (S) to RV weights) and to assess mRNA expression level of ?1- and ?2-adrenoceptors, muscarinic m1 and m2 receptors, and vascular endothelial growth factor (VEGF). Resting HR was significantly lower in rats than in pikas and increased after AT injection only in rats. IsoP injection induced a significant increase in HR in rat for all doses, which was systematically greater than in pikas. In pikas HR was slightly increased only after the two highest concentrations of IsoP. Fulton's ratio was greater in rats compared with pikas but the LV + S adjusted for body weight was greater in pikas. Pikas showed lower ?1-adrenoceptors and muscarinic m2 receptors mRNA expression but larger VEGF mRNA expression than rats both in RV and LV. These results suggest that pikas have a lower maximal HR compared with rats certainly due to a decrease in ?-adrenergic and muscarinic receptors mRNA expression. However, the LV hypertrophy probably led to an increase in stroke volume to maintain cardiac output in response to the cold and hypoxic environment.

SUBMITTER: Pichon A

PROVIDER: S-EPMC3831927 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Cardiac adaptation to high altitude in the plateau pika (Ochotona curzoniae).

Pichon Aurélien A Zhenzhong Bai B Marchant Dominique D Jin Guoen G Voituron Nicolas N Haixia Yun Y Favret Fabrice F Richalet Jean-Paul JP Ge Ri-Li RL

Physiological reports 20130718 2

The aim of this study was to assess maximal heart rate (HR) and heart morphological changes in high altitude living "plateau pikas" and rats bred at 2260 m. Rats and pikas were catheterized to measure HR (2260 m). After baseline measurements, 1 mg/kg of atropine (AT) and increasing doses of isoproterenol (IsoP) (0.1, 1, 10, and 100 μg kg) were injected into animals. Right (RV) and left ventricles (LV) were removed to calculate Fulton's ratio (LV + septum (S) to RV weights) and to assess mRNA exp ...[more]

PMID: 24303117

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Project description:Testis-specific lactate dehydrogenase (LDH-C₄) is one of the lactate dehydrogenase (LDH) isozymes that catalyze the terminal reaction of pyruvate to lactate in the glycolytic pathway. LDH-C₄ in mammals was previously thought to be expressed only in spermatozoa and testis and not in other tissues. Plateau pika (Ochotona curzoniae) belongs to the genus Ochotona of the Ochotonidea family. It is a hypoxia-tolerant species living in remote mountain areas at altitudes of 3000-5000 m above sea level on the Qinghai-Tibet Plateau. Surprisingly, Ldh-c is expressed not only in its testis and sperm, but also in somatic tissues of plateau pika. To shed light on the function of LDH-C₄ in somatic cells, Ldh-a, Ldh-b, and Ldh-c of plateau pika were subcloned into bacterial expression vectors. The pure enzymes of Lactate Dehydrogenase A₄ (LDH-A₄), Lactate Dehydrogenase B₄ (LDH-B₄), and LDH-C₄ were prepared by a series of expression and purification processes, and the three enzymes were identified by the method of sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and native polyacrylamide gel electrophoresis (PAGE). The enzymatic kinetics properties of these enzymes were studied by Lineweaver-Burk double-reciprocal plots. The results showed the Michaelis constant (Km) of LDH-C₄ for pyruvate and lactate was 0.052 and 4.934 mmol/L, respectively, with an approximate 90 times higher affinity of LDH-C₄ for pyruvate than for lactate. At relatively high concentrations of lactate, the inhibition constant (Ki) of the LDH isoenzymes varied: LDH-A₄ (Ki = 26.900 mmol/L), LDH-B₄ (Ki = 23.800 mmol/L), and LDH-C₄ (Ki = 65.500 mmol/L). These data suggest that inhibition of lactate by LDH-A₄ and LDH-B₄ were stronger than LDH-C₄. In light of the enzymatic kinetics properties, we suggest that the plateau pika can reduce reliance on oxygen supply and enhance its adaptation to the hypoxic environments due to increased anaerobic glycolysis by LDH-C₄.

Dataset Information

Cardiac adaptation to high altitude in the plateau pika (Ochotona curzoniae).

Publications

Cardiac adaptation to high altitude in the plateau pika (Ochotona curzoniae).

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